COAGULATION. 461 



peptone-plasma or bird's plasma, both of which owe their relative 

 incoagulability to the presence of an excess of antithrombin. 



Theory of Coagulation. Modern theories of coagulation, with 

 some exceptions (Wooldridge, Nolf), accept as their starting-point 

 'the fact that fibrin is formed eventually by the action of thrombin 

 upon fibrinogen. The various theories proposed differ from one 

 another largely in their explanation of the origin of the thrombin 

 and of the parts taken by the calcium and the thromboplastic 

 substances in the process df clotting. The simplest of these 

 theories assumes that the prothrombin in the blood arises from the 

 blood-plates (and leucocytes ?) and is activated to thrombin by 

 the calcium, the thrombin then reacting with the fibrinogen. The 

 theory which seems to be most generally accepted at present is 

 that proposed independently by Morawitz* and by Fuld and Spirof 

 Using the terminology of Morawitz, this theory assumes that the 

 thrombin is present in the blood in an inactive form which .he 

 designates as thrombogen. To convert this thrombogen (pro- 

 thrombin) to thrombin requires the action both of calcium salts 

 and of an organic thromboplastic substance which he designates 

 as a kinase or thrombokinase. Thrombokinase is furnished by the 

 tissue-cells in general, especially by those rich in nuclein, and is 

 furnished also by the cellular elements of the blood. In the cir- 

 culating blood calcium salts and thrombogen are present, but no 

 kinase. When the blood is shed the disintegration of the platelets 

 and leucocytes, in mammalian blood, or of the cells of the wounded 

 tissues in the blood of the lower vertebrates, liberates thrombo- 

 kinase, which then, in combination with the calcium, converts the 

 thrombogen to thrombin. The theory may be expressed in dia- 

 grammatic form as follows: 



Cellular elements * thrombokinase 



Thrombokinase -I- calcium + thrombogen = thrombin 



Thrombin + fibrinogen = fibrin. 



The theory explains very well many of the most significant 

 facts known in regard to clotting, but it may be said that the cen- 

 tral feature of the theory, the existence of an organic kinase, has 

 not been supported by direct experimental evidence. The author 

 has been led by his own workj to adopt a different point of view, 

 which may be expressed briefly, as follows: Prothrombin may be 

 converted to active thrombin by the action of calcium alone. 

 This activation does not occur in the circulating blood because an 



* Morawitz, Hofmeister's "Beitrage," 5, 133, 1904, and "Arch. f. klin. 

 Med.," 79, 1. 



t Fuld and Spiro, "Hofmeister's Beitrage," 5, 174, 1904. 



t Howell, loc. tit. and "American Journal of Physiology," 29, 187, 1911. 



